Impaired Oral Glucose Tolerance Test Research Articles

The sonographic picture of an echogenic liver is an indicator of pathologic glucose tolerance

Almost all patients in departments of internal medicine routinely undergo abdominal ultrasound examination in which liver changes indicating hepatic steatosis are often detected. The aim of this study was to assess the occurrence of pathological oral glucose tolerance, manifest diabetes mellitus and other changes indicative of a metabolic syndrome in patients with sonographic signs of hepatic steatosis. 577 patients were examined during a period of 6 months: 90 patients fulfilled the inclusion criteria. Among the 90 patients with echodense liver who were included in the study (42 female, 48 male) 36 patients presented with previous diagnosis of diabetes mellitus (40%). The oral glucose tolerance test was impaired in 19 patients (21%) and in four patients with manifest diabetes mellitus (4%). Among patients with echodense liver a high percentage presented with obesity and impaired fat metabolism. The large number of patients with an impaired oral glucose tolerance test converting to manifest diabetes, as well as the large number of patients with manifest disorders of fat metabolism suggest that screening for diabetes should be performed in patients who present with sonographic signs of hepatic steatosis.

Impaired functional vasodilation in obese Zucker rats: role of insulin resistance and inflammation

Obesity is characterized by insulin resistance (IR) and chronic inflammation, which may alter cyclooxygenase‐2 (COX‐2) activity and thus arachidonic acid (AA) metabolism. The obese Zucker rat (OZR) is a model of IR with increased inflammatory markers. We have shown an impaired functional vasodilation (FD) in the OZR due to altered arachidonic acid (AA) metabolism and increased thromboxane receptor (TP) activation. We hypothesize that IR alters AA metabolism via stimulation of COX‐2, resulting in impaired FD. Male lean (LZR) and OZR were treated with rosiglitazone (ROZ, 5mg/kg/day, rat chow) for 2 wks. The arteriolar diameters were measured in spinotrapezius muscle following muscle stimulation without and with the selective COX‐2 inhibitor NS‐398 or the TP antagonist SQ 29548 (SQ). Compared to LZR, untreated OZR exhibited an impaired oral glucose tolerance test and a two fold COX‐2 expression, both of which were normalized by ROZ treatment. The impaired FD in OZR was improved by 88% after acute treatment with NS‐398 and by 50% after chronic treatment with ROZ. SQ improved the vasodilatory responses by 58% in untreated OZR with no effect in lean or ROZ treated OZR. These results suggest that the increased TP activation and impaired FD in OZR is due to IR‐stimulated increase in COX‐2 activity. (Supported by AHA 55841, 53952, HL 51971)

Frequency of impaired oral glucose tolerance test in high risk pregnancies for gestational diabetes mellitus.

To determine the frequency of impaired oral glucose tolerance test in high risk pregnancies for Gestational Diabetes Mellitus (GDM). Cross-sectional study. The study was conducted in Obstetric Ward and outpatient department, at Baqai Hospital, Nazimabad and Fatima Hospital, Baqai Medical University, Karachi, from May to October 2005. A total of 50 high risk pregnancies for gestational diabetes mellitus were selected through outpatient department of obstetrics. Data was collected according to certain obstetric and non-obstetric risk factors for GDM as inclusion criteria through a designed proforma i.e. family history of diabetes, macrosomia (i.e, wt > 3.5 kg), abortions, grand multiparity, a sudden increase in weight (>1 kg/wk) during pregnancy, age > 35 years, early neonatal deaths/sudden IUDS, polyhydramnios, urogenital infections (vulvo-vaginal candidiasis and UTI), previous history of GDM, congenital abnormalities (with or without polyhydramnios) and multiple pregnancy. Oral glucose tolerance test was performed and analyzed according to American Diabetic Association criteria, 2004. The most frequent risk factors were family history of diabetes mellitus in 1st degree relative and large-for-dates babies in 18 patients. Similarly, high risk factors such as history of abortions and grand multiparity were present in 16 and 14 pregnant women respectively. Least common factors, which contributed for GDM, were polyhydramnios in 4 cases and perinatal mortality (due to congenital anomalies of foetus, intrauterine deaths or neonatal deaths) seen only in 5 cases. Overall impaired oral glucose tolerance test was found in 24%. Most patients had one (17%) or two risk factors commonly (23%). Only 2% had shown five or more risk factors. Oral glucose tolerance test is a useful diagnostic tool to detect GDM in high risk pregnancies, depending upon the high frequency of number of risk factors in each individual.

A comparison of sural nerve conduction studies in patients with impaired oral glucose tolerance test

Monitoring of the sural nerve is a sensitive method for detection of neuropathies. We examined different methods of studying sural nerve conduction in a group of patients with impaired glucose tolerance (IGT) in the same study. Several parameters of sural nerve were investigated in 20 patients. First, sensory nerve conduction studies of the sural nerve were performed on the distal-leg and the proximal-leg segments. Second, dorsal sural nerve studies were conducted. Third, the sural/radial sensory nerve action potential (SNAP) amplitude ratios were calculated. The results were compared with those obtained from 21 healthy controls. Abnormal results revealing peripheral neuropathy were found in only one patient and dorsal sural SNAP was absent in another patient (5%). Although the results of nerve conduction studies were within normal ranges except the patient with peripheral neuropathy, the lower extremity nerves and especially sural nerves have been found to be more affected and the parameters revealed large differences between groups (P < 0.05). Only dorsal sural nerve latency related to fasting blood glucose level in patients (<0.05). Sural nerve studies should be of value to determine neuropathy in IGT patients. This study supported the idea that IGT is a transitional state before diabetes and also the importance of the dorsal sural nerve latencies for early detection of neuropathy.

Diabetes and lipid disorders

Glucose homeostasis is impaired in girls and women with Turner syndrome. A decreased insulin sensitivity as well as a reduced β-cell function seems to play a role. Impaired oral glucose tolerance test is found in up to 78% of study populations. An epidemiological study have found a relative risk of type 1 diabetes of 11.6 and type 2 diabetes of 4.4 in Turner syndrome.

Effects of digitonin on hyperglycaemia and dyslipidemia induced by high-sucrose intake

This study examined whether high-sucrose intake effects on lipid profile and oral glucose tolerance may be inhibited by a single administration of digitonin, a saponin from the seeds of Digitalis purpurea Male Wistar 24 rats were initially divided into two groups ( n = 12): (C) was given standard chow and water; (S) received standard chow and 30% sucrose in its drinking water. After 30 days of treatments, C rats were divided into two groups ( n = 6): (CC) given an intra-gastric dose 0.5 mL saline; (CD) given a single intra-gastric dose of 15 mg/kg digitonin. S rats were also divided into two groups ( n = 6): (SC) given intra-gastric saline and (SD) given digitonin. Rats were sacrificed after the oral glucose tolerance test (OGTT) at 2 h after the digitonin administration. S rats had higher total energy intake and final body weight than C. SC rats had fasting hyperglycaemia and impaired OGTT. Digitonin in SD group improved the glucose tolerance. Triacylglycerol (TG), very-low-density lipoprotein (VLDL-C) and free fatty acid (FFA) serum concentrations were increased in SD rats from CC. Digitonin in SD rats decreased FFA and led TG and VLDL-C concentrations at the levels observed in the CC group. Despite the enhanced cholesterol in CD group from CC, the high-density lipoprotein (HDL-C) was increased in these animals. HDL-C/TG ratio was higher in CD and SD than in CC and SC, respectively. No significant differences were observed in lipid hydroperoxide(LH) between the groups. VLDL-C/LH ratio and gamma-glutamyl transferase (GGT) activity were increased in SC group and were decreased in SD rats from the SC. In conclusion digitonin enhanced glucose tolerance and had beneficial effects on serum lipids by improve antioxidant activity.

Effects of lamivudine therapy on the glucose metabolism in children with chronic hepatitis B: first year follow-up results

Although the most common major toxicity of lamivudine has been pancreatitis, there is no report investigating possible impaired pancreatic functions, including glucose intolerance due to lamivudine therapy. The aim of this study was to evaluate the effects of lamivudine on the glucose metabolism in children. Twenty-three children were included: eight patients were treated with lamivudine, others with both lamivudine and interferon-alpha. An oral glucose tolerance test (OGTT) was performed before the treatment, and after 6 and 12 months. After 6 and 12 months of the treatment four (18.4%) and eight (34.8%) patients had impaired OGTT, respectively. We did not find any relationship between impaired OGTT and age, gender, elevated amylase, abdominal pain and the mode of therapy (P>0.05). While mean glucose value after 2 h was higher than that of baseline, mean insulin concentrations and area under the curve values were not different (P<0.0001, P>0.05, and P>0.05, respectively). This is the first report demonstrating that lamivudine may impair the OGTT. Since at least 8.7% of our patients had persistently impaired OGTTs during the first year of the therapy, it may be reasonable to screen children before lamivudine therapy is started.

Effect of PPAR-Γ agonist-rosiglitazone-on adiponectin level in the metabolic syndrome

The metabolic syndrome is associated with significant cardiovascular morbidity and mortality. Adiponectin is an adipocytokine that possesses anti-diabetic, anti-atherogenic and anti-inflammatory properties which collectively establish its unique vascular protective role. In addition, thiazolidinediones (TZDs) improve glucose tolerance and insulin sensitivity in animal models of insulin resistance. Therefore we studied the effect of rosiglitazone on adiponectin levels in the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat model. 20 male Sprague-Dawley rats were fed a fructose-enriched diet for 3 weeks.Ten rats continued to consume the Fructose diet for another 2 weeks, while the other 10 received rosiglitazone (10mg/kg) in their drinking water on top of the fructose. Blood pressure (BP), oral glucose tolerance test (OGTT), plasma insulin, triglycerides and adiponectin levels were measured at baseline, after 3 weeks and at the end of the experiment. Visceral fat tissues were taken from all animals after 5 weeks and the expression of adiponectin mRNA was determined by quantitative RT-PCR. Fructose feeding led to significant increase in BP, insulin and triglyceride levels and to impaired OGTT. Adiponectin plasma level did not change significantly. Treatment with rosiglitazone, however, lowered BP, improved OGTT and resulted in significant increase in adiponectin plasma level (from 5.9±2.2 to 18.3±5μg/ml). Adiponectin mRNA expression in visceral fat increased 3.5 fold following rosiglitazone treatment. This study shows for the first time in an animal model which displays most of the metabolic syndrome components, that the insulin sensitizer rosiglitazone induced elevation of plasma level of adiponectin due to an increase in gene expression. Whether this is the mechanism through which rosiglitazone exerts its beneficial effect remains to be studied.

Tumor-induced changes in host metabolism: a possible role for free tryptophan as a marker of neoplastic disease.

Tumor growth is associated with a number of metabolic abnormalities. Glucose metabolism is deranged as frequently revealed by an impaired oral glucose tolerance test. Lipoprotein lipase activity is depressed, resulting in hypertrigliceridemia after an exogenous lipid load. Also protein metabolism is deranged in cancer patients, as revealed by changes of plasma amino acid profile. Our previous studies on plasma amino acids have shown that increased plasma free tryptophan levels are a frequent finding in cancer patients. To sustain a possible role for free tryptophan as a marker of neoplastic disease, we measured its plasma concentrations in 241 patients with cancer. Plasma free tryptophan concentrations were found to be significantly elevated with respect to healthy controls in patients with breast, lung, colon, stomach, and cancer from various origin. The sensitivity of this marker in predicting the presence of the tumor was highest for stomach and lung cancer patients. High plasma free tryptophan concentrations seem to be directly related to the presence of the tumor, since in breast cancer patients they returned to within normal range after eradicative surgery.

Lundh meal: a single non-invasive challenge test for evaluation of exocrine and endocrine pancreatic function in cystic fibrosis patients.

The determination of endocrine and exocrine pancreatic function in cystic fibrosis patients is clinically important. Recently, a new non-invasive test, in which pancreatic stimulation by a Lundh meal is followed by sequential serum lipase measurements, was found to be a good indicator of exocrine pancreatic status. Since the Lundh meal also contains glucose, the present study assessed whether it also might be suitable for evaluation of the pancreatic endocrine axis. After an overnight fast, 10 healthy non-diabetic subjects and 14 cystic fibrosis patients ingested a Lundh meal. Glucose, insulin, and C peptide levels were measured at various time intervals following the meal. For purposes of comparison, the oral glucose tolerance test was also performed on the cystic fibrosis patients. All healthy subjects demonstrated an increase in glucose levels post Lundh meal, peaking at 45 min (mean 140+/-21 mg/dl) and then gradually declining and reaching the normal range at 120 min. Concordant peaks of insulin (46.3+/-20 IU/ml) and C peptide (5.8+/-1. 5 ng/ml) levels were noted at 60 min. All 14 cystic fibrosis patients had normal basal glucose levels: in 8, the pattern of glucose, insulin, and C peptide post Lundh meal was similar to that of the healthy controls. These 8 patients also had a normal oral glucose tolerance test, and their hemoglobin A(1C) levels were within the normal range. The other 6 cystic fibrosis patients demonstrated glucose levels above 200 mg/dl 30-60 min post Lundh meal, and all also had an impaired oral glucose tolerance test. Of these 6, 4 had high levels of hemoglobin A(1C). This study demonstrates that the Lundh meal challenges the endocrine pancreas as well as the oral glucose tolerance test. Thus, determination of both exocrine and endocrine pancreatic status can be achieved by a single non-invasive test.

Beneficial effect of intravenous bolus of corticotropin-releasing factor on glucose intolerance of genetically obese (fa/fa) rats.

The effect of an ovine corticotropin-releasing factor (oCRF) bolus administered intravenously at the onset of glucose ingestion during oral glucose tolerance tests (OGTTs) was evaluated in conscious lean (FA/FA) and genetically obese (fa/fa) rats. When the amount of oCRF was purposely small to not stimulate the hypothalamo-pituitary-adrenal (HPA) axis, it normalized the glucose intolerance of genetically obese rats as tested during OGTTs and decreased their insulin output, whereas it had no effect in lean rats. In obese rats, plasma xylose levels measured after the ingestion of a xylose load were unaltered by the intravenous oCRF bolus, indicating that the beneficial effect of oCRF on glucose intolerance of fa/fa rats was unlikely to be dependent on glucose absorption. When the intravenous bolus of oCRF was doubled at the onset of OGTTs, it stimulated the HPA axis and produced a worsening of glucose intolerance in obese rats together with an increase in their insulin response. Again, it had no effect in lean rats. The abnormal intravenous glucose tolerance of obese rats was unaffected by the administration of an oCRF bolus: This is in keeping with previous data showing that bypassing the oral cavity fails to elicit several sensory reflexes that markedly influence subsequent glucose clearance. It has been suggested that obese rats may have deficient oropharyngeal reflexes that could be reactivated by the oCRF bolus, thereby being responsible for the normalization of their impaired OGTT, which lies in the hepatic glucose production process.

Oral glucose tolerance testing in cystic fibrosis: Correlations with clinical parameters and glycosylated haemoglobin determinations

In 48 patients (age 2-28 years) with documented cystic fibrosis, glucose tolerance was evaluated by means of an oral glucose tolerance test (OGTT) and repeated glycosylated haemoglobin (HbA1C) measurements. An impaired OGTT was found in 15 patients. Their degree of undernutrition and severity of lung and liver involvement were no different from those with normal glucose tolerance. The mean peak insulin concentration as well as the integrated insulin concentration during the OGTT were comparable with patients with normal glucose tolerance (GT) and those with an impaired tolerance (GI). The mean time to attain peak insulin levels was significantly delayed in the GI group. (117 min vs 86 min P less than 0.01). On initial testing, elevated HbA1C levels were found in 22 patients. Mean HbA1C levels in the GI group were higher than in the GT group (8.2% vs 7.5% P less than 0.01). The HbA1C levels at the moment of OGT testing were positively correlated with the glycaemic response during the OGTT. The repeated HbA1C measurements 1 year later were no different from the initial mean HbA1C values in both groups. Two GI patients with initial HbA1C levels of 7.5% and 11% respectively developed diabetes mellitus several months after testing. The need for serial HbA1C determinations in cystic fibrosis is questioned.

Glucose homeostasis in mucoviscidosis

In patients with cystic fibrosis (CF) of the pancreas an endocrine imbalance especially of insulin secretion due to progressive structural abnormalities of the pancreas must be expected. 30-75 percent of CF-patient exhibit impaired oral glucose tolerance tests (oGTT). Deterioration of the glucose homeostasis leads to a secondary diabetes mellitus that mimics a type II diabetes in the early stage, in the later course of disease it resembles a type I diabetes with absolute insulinopenia. In this study glucose homeostasis was investigated after an oral glucose load with 1.75 g glucose/kg bodyweight. Glucose, C-peptide and insulin were measured during 180 minutes. 32 nondiabetic CF-patients were studied. 16 patients revealed an impaired oral glucose tolerance according to the criteria of the National Diabetes Data Group. 6 patients showed a normal glucose tolerance and 10 patients with normal fasting and 120 minute glucose concentrations were hyperglycemic at midtest determinations. Impaired oGTTs were observed in malnourished CF-patients in a higher rate than in normal weight patients. A delayed and exceeded C-peptide and insulin response to the oral glucose load was determined with deteriorating glucose tolerance. Glucose values did not drop to fasting values at the 180 minute determination in cases of impaired oral glucose tolerance.

Insulin resistance in Cushing's syndrome.

It is well established that cortisol excess causes insulin resistance in man, but the mechanisms responsible for this insulin resistance are poorly understood. We studied five women with Cushing's syndrome with impaired oral glucose tolerance tests and seven normal subjects, plotting the shape of the insulin-induced disposal dose-response curve obtained by means of the euglycemic clamp procedure during four different plasma insulin plateaus at four infusion rates of 21, 73, 760, and 1200 mU/M2 . min. Glucose disposal (M = mg/M2 . min) was calculated as glucose amount infused to maintain euglycemia. In Cushing's syndrome the dose-response curve was shifted to the right in comparison with normal subjects, with a significantly lower M (337 +/- 35 vs. 657 +/- 76 P less than 0.01) during the highest insulin infusion rate [maximal glucose disposal (MGD)] without any significant difference in the levels of insulin half-maximally effective in the stimulation of glucose utilization. Neither erythrocyte nor monocyte maximum insulin receptor binding were different between the two populations. Four Cushing's syndrome patients were studied again after surgical treatment. A marked improvement of MGD was observed without any significant change in insulin-binding capacity. These results, particularly the marked decrease in MGD, a typical feature of postreceptor defects, indicate that cortisol-induced insulin resistance in man is due to an impairment of peripheral insulin action located beyond the hormone-receptor binding step.

HbA1 and beta cell function in cystic fibrosis (CF)

The increase in the longevity of patients with CF appears to have been accompanied by a rise in the frequency of glucose intolerance. HbA1 blood conc. is an objective mean to assess carbohydrate homeostasis. HbA1 conc. were examined in 34 CF patients aged 1½-20½ years. In 11 oral glucose tolerance tests (OGTT) were performed and glucose and insulin conc. were measured. The mean HbA1 conc. in CF children (n=34) was 7.97±0.2 (mean±SEM) and significantly higher than that in normal children - 6.8±0.13 (n=40) (mean±SEM), although there was no difference in the fasting blood glucose between the two groups.8 children had a normal, while 3 children had an impaired OGTT. These latter 3 children had a delayed peak response in insulin levels, while there was a decrease in the level of the insulin response in all the children. No correlation was found between HbA1 conc. and the age of the patients, nor between HbA1 and the clinical status (Shwachman score).In summary, severe insulinopenia in children with CF is not always accompanied by an increment in HbA1, although serial determinations of the level of HbA1 may reveal deterioration in glucose tolerance.

Influence of lactation on oral glucose tolerance in the puerperium.

The influence of endogenous hyperprolactinaemia on oral glucose tolerance in normal women post-partum was studied. An oral glucose tolerance test (OGTT) was performed 8 weeks after delivery in 23 women, 13 of whom were breastfeeding. The lactating women had significantly higher plasma prolactin values before and during the OGTT than the non-lactating women (P less than 0.005). Fasting values of serum FSH, LH, progesterone and plasma glucagon were similar in the two groups. The non-lactating women had higher fasting concentrations of serum oestradiol (P less than 0.0005), plasma glucose (P less than 0.05) and insulin (P less than 0.05) than the lactating women. After oral glucose no differences were found between lactating and non-lactating women in changes in plasma glucose, insulin and glucagon concentrations. It is concluded that lactating women 8 weeks post-partum do not have an impaired OGTT compared to non-lactating women despite elevated plasma prolactin levels.

Insulin release, insulin sensitivity, and glucose intolerance.

Groups of subjects with different degrees of glucose intolerance were examined in order to determine, first, the capacity of the beta cells to release insulin upon glucose stimulation and, second, sensitivity to insulin. The groups were selected on the basis of fasting blood glucose value and tolerances to oral and intravenous glucose administration. The body weights, ages, and sexes of the subjects were well matched with those of control subjects with normal tolerances to oral and intravenous glucose administration. Computer analysis of the glucose and insulin curves during a standardized glucose infusion test made possible the measurement of the initiatory (parameters KI and IP) and potentiatory (parameter KP) effects of glucose on insulin release and of the sensitivity to endogenous insulin (parameter KG). In subjects with impaired oral but normal intravenous glucose tolerance tests, KG was decreased, KP was increased, and KI and IP were normal. However, in these subjects, KI and IP were considerably lower than in a matched group of control subjects with the same decrease in KG but with normal oral and intravenous glucose tolerance tets. In subjects in which both oral and intravenous glucose tolerance tests were impaired and in subjects with mild manifest diabetes, KI, IP, and KG were decreased whereas KP was normal. These data suggest that all stages of glucose intolerance are accompanied by a decreased ability of glucose to initiate insulin release and by decreased sensitivity to insulin. These derangements seem to be partially compensated for by enhancement of the capacity of glucose to potentiate insulin release in subjects with decreased oral but normal intravenous glucose tolerance tests.